Abstract
The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated. In the present study, we aimed to investigate the effects of BP on placenta-derived mesenchymal stem cells (PD-MSCs) in vitro. We found that the AhR in PD-MSCs was expressed under the treatment of BP, and its activation markedly disrupted osteogenic differentiation through the alteration of stemness activity of PD-MSCs. Moreover, BP treatment significantly reduced the proliferation activity of PD-MSCs and expression of pluripotent markers through the induction of AhR. Treatment with StemRegenin 1 (SR1), a purine derivative that antagonizes the AhR, effectively prevented BP-induced reduction of the proliferation and differentiation activity of PD-MSCs. In this study, we found that BP treatment in PD-MSCs markedly obstructs PD-MSC stemness through AhR signaling. Noteworthy, SR1-mediated MSC application will contribute to new perspectives on MSC-based therapies for air pollution-related bone diseases.
Highlights
Environmental pollutants are associated with the increased risk of various health problems such as cancer as well as cardiovascular and/or pulmonary diseases in humans
These results revealed that BP does not have a dosage-dependent effect on placenta-derived mesenchymal stem cells (PD-Mesenchymal stem cells (MSCs))
In order to determine whether the results are specific to PD-MSCs, bone marrow-derived mesenchymal stem cells (BM-MSCs) were tested under the same conditions
Summary
Environmental pollutants are associated with the increased risk of various health problems such as cancer as well as cardiovascular and/or pulmonary diseases in humans. PAHs are known potent agonists of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved in the modulation of biological responses to aromatic hydrocarbons [2]. AhR activation leads to the inhibition of growth and differentiation of endometrial epithelial cells and liver progenitor cells, and the AhR modulates cellular function, including cell death, growth, and differentiation [3, 4]. BP, one of the most intensively studied pollutants, has been considered a potentially carcinogenic substance and an important risk factor for cardiovascular diseases [5, 6]. Environmental pollution, such as BP from cigarette smoking, has
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